Many mental and neurological disorders - including frontotemporal dementia, obsessive-compulsive disorder, major depression and drug addiction - can be broadly characterized as patients making poor choices. While these disorders disrupt choice behavior in a variety of domains - including food, money, intertemporal choices, social choices, etc. - deficits can be unitarily described as affecting choices based on subjective preferences, where no intrinsically correct option exists. This behavior is referred to as economic choice (EC). As a mental process, EC entails assigning values to the available options - a decision is then made by comparing values. The overarching goal of this research proposal is to understand at the neuronal level how values are computed and compared during EC, and how choice outcomes are transformed into suitable actions. Much work in recent years examined the neural encoding of subjective value, defined by the integration of multiple determinants (a commodity, its quantity, the motivational state, time delays, etc.). The emerging consensus based on neurophysiology, imaging and lesion studies is that choices might be based on values computed in the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (vmPFC). Key questions remain, however, open. Notably, neurons in the OFC encode value independently of the visuomotor contingencies of choice (in goods space). However, most choices eventually lead to an action. Moreover, different options are often associated with actions bearing different costs. Thus a broad issue is how the abstract representation of value in OFC relates to neural activity underlying action planning. Using a task that dissociates economic choice from action planning, we will address two specific questions. First, we will examine the neuronal mechanisms through which the choice outcome the chosen good guides an action plan. Anatomical considerations and preliminary results suggest that this good-to-action transformation involve the lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC). Second, we will examine whether and how action costs are integrated with other determinants of value. In addition, we will address a discrepancy in the literature between monkey neurophysiology studies (which generally found cells encoding subjective values in OFC but not in vmPFC) and human imaging studies (most of which emphasized value signals in vmPFC). We hypothesize that this discrepancy might be partly due to the fact that vmPFC activity is highly correlated with autonomic responses, which are strong during decision making but subside after training. These issues will be addressed using single cell recordings and reversible inactivation in monkeys performing economic choices. In recent years, we developed a new approach to study the neurobiology of valuation and EC that has proven both fruitful and influential. By addressing some of the most pressing and open questions, this research may shape our understanding of the neural mechanisms that underlie EC and that malfunction in mental illness. PUBLIC HEALTH RELEVANCE: This research project will investigate how neuronal activity in different regions of the frontal lobe underlies economic choice - a behavior specifically disrupted in drug addiction and mental disorders such as frontotemporal dementia, obsessive-compulsive disorder and major depression.